Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study
Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study
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DOI：
10.1128/msphere.00716-19
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发表时间：
2019-09-01
期刊：
影响因子：
4.8
通讯作者：
Permar, Sallie R.
中科院分区：
文献类型：
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作者：
Hompe, Eliza D.;Jacobson, Denise L.;Permar, Sallie R.
为了设计能够与抗逆转录病毒疗法（ART）协同作用的免疫干预措施，以降低艾滋病毒母婴传播（MTCT）率，有必要确定怀孕和哺乳期间抗逆转录病毒疗法背景下孕产妇免疫反应的特征，并确定其对母婴传播的影响。先前的研究报道了母乳包膜（Env）特异性抗体和抗体依赖性细胞毒性（ADCC）活性与产后传播减少之间的关联。在这项研究中，我们在一项匹配的病例对照研究中调查了这些免疫相关因素是否与母乳喂养期间接受母体抗逆转录病毒治疗或婴儿奈韦拉平预防的母婴对的保护类似，该研究是在国际孕产妇-儿科-青少年艾滋病临床试验网络（PROMISE）试验中进行的。利用经母体血浆病毒载量调整后的条件logistic回归模型评估19名有病毒传播母亲和57名无病毒传播母亲的产后传播风险。产后MTCT对免疫相关增加1个单位的比值比为母乳env特异性分泌IgA (sIgA) 3.61(95%可信区间[CI]， 0.56, 23.14)，母乳为2.32 (95% CI, 0.43, 12.56)，血浆env特异性IgA为2.16 (95% CI, 0.51, 9.14)，母乳为4.57 (95% CI, 0.68, 30.48)，血浆ADCC活性为0.96 (95% CI, 0.25, 3.67)，所有CI均为1.0。有趣的是，尽管未经治疗的hiv感染妇女的粘膜IgA反应较差，但在该队列中，母乳和血浆env特异性IgA的量之间存在很强的相关性。在这项具有里程碑意义的PROMISE研究中，对少量出生后病毒传播的分析表明，没有单一抗体应答与母乳传播风险相关。尽管有抗逆转录病毒治疗，每年仍有150万名婴儿通过母婴传播新感染艾滋病毒-1，其中高达42%的感染发生在母乳喂养期间。有几个因素导致儿童持续感染，包括抗逆转录病毒治疗不坚持、耐药艾滋病毒毒株的出现、母乳喂养期间的急性感染以及资源有限地区难以获得抗逆转录病毒治疗。更好地了解在抗逆转录病毒治疗环境中提供保护以防止产后传播的孕产妇体液免疫反应，对于指导设计进一步消除产后艾滋病毒传播的孕产妇疫苗战略至关重要。在这项研究中，我们发现在怀孕期间接受抗逆转录病毒治疗的妇女，血浆病毒载量与母乳和血浆IgA反应呈正相关；然而，由于样本量小，有关MTCT风险的结论受到限制。这些发现将为未来的研究提供信息，以调查能够与抗逆转录病毒治疗协同消除母乳喂养期间母婴传播的母体免疫干预措施。
To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibody-dependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk.IMPORTANCE Each year, >150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.